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generation of recombinant vaccinia viruses expressing puumala virus proteins and use in isolating cytotoxic t cells specific for puumala virus.puumala (puu) virus causes a form of hemorrhagic fever with renal syndrome (hfrs), called nephropathia epidemica (ne), in europe. hfrs is characterized by an increased capillary permeability, which we hypothesize is caused by hyperactivation of the host immune system, especially cellular immune responses. to identify cytotoxic t lymphocytes (ctls) specific for the puu virus from ne patients, we have made recombinant vaccinia viruses expressing puu virus proteins, the nucleocapsid (n) and two sur ...200211900840
hantavirus nucleocapsid protein interacts with the fas-mediated apoptosis enhancer daxx.hantaviruses cause two severe diseases, haemorrhagic fever with renal syndrome in eurasia and hantavirus pulmonary syndrome in the americas. to understand more about the molecular mechanisms that lead to these diseases, the associations of puumala virus nucleocapsid protein (puuv-n) with cellular proteins were studied by yeast two-hybrid screening. daxx, known as an apoptosis enhancer, was identified from a hela cdna library and its interaction with puuv-n was confirmed by gst pull-down assay, c ...200211907324
acute disseminated encephalomyelitis following nephropathia epidemica.acute disseminated encephalomyelitis (adem) is an acute monophasic inflammatory and demyelinating disease of the central nervous system (cns) occurring days to weeks after a virus infection or vaccination. nephropathia epidemica (ne) is a haemorrhagic fever with renal syndrome caused by puumala virus, with endemic regions in europe, especially scandinavia and western russia. we describe a case of severe nephropathia epidemica requiring dialysis, followed by severe cns symptoms caused by adem. to ...200211939950
mapping of b-cell epitopes in the nucleocapsid protein of puumala hantavirus.hantavirus nucleocapsid protein (n) has been proven to induce highly protective immune responses in animal models. the knowledge on the mechanisms behind n-induced protection is still limited, although recent data suggest that both cellular and humoral immune responses are of importance. for a detailed b-cell epitope mapping of puumala hantavirus (puuv) n, we used recombinant n derivatives of the russian strain cg18-20 and the swedish strain vranica/hällnäs, as well as overlapping synthetic pept ...200211952140
tula hantavirus in belgium.european common voles (microtus arvalis), captured in belgium in 1999, were proven by molecular as well as by serological techniques to be infected with tula hantavirus (tulv). this is the first evidence for the presence of tulv in this country. no indication of spill-over infections of puumala virus, known to be highly endemic among bank voles (clethrionomys glareolus) within the same geographical regions as the trapped tulv-infected common voles, was observed. together with previous reports on ...200212002543
cross-protection against challenge with puumala virus after immunization with nucleocapsid proteins from different hantaviruses.hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome in humans. the nucleocapsid protein (n) is relatively conserved among hantaviruses and highly immunogenic in both laboratory animals and humans, and it has been shown to induce efficient protective immunity in animal models. to investigate the ability of recombinant n (rn) from different hantaviruses to elicit cross-protection, we immunized bank voles with rn from puumala (puuv) ...200212050380
hypophyseal hemorrhage and panhypopituitarism during puumala virus infection: magnetic resonance imaging and detection of viral antigen in the hypophysis.we describe 3 cases of nephropathia epidemica (ne) that confirm that puumala virus infection may cause hypophyseal injury. autopsy revealed a hemorrhagic hypophysis positive for puumala virus antigen in both neuroendocrine stromal and vascular endothelial cells in 1 patient, and 2 patients developed hypophyseal hemorrhage (diagnosed with magnetic resonance imaging) during or shortly after acute ne, both of whom developed panhypopituitarism.200212060884
[epidemic nephropathy. an important differential diagnosis of acute renal failure in reutlingen, an endemic area].hantavirus ("epidemic") nephropathy (hn), or hemorrhagic fever with renal syndrome (who nomenclature), is an infection caused by strains (e.g. puumala) of hantavirus, which is often accompanied by acute renal failure. although its typical symptomatology has been fully reported, it is rarely included in the differential diagnosis of renal nephropathy. this study investigated whether, in the presence of typical symptoms, specific search for a certain constellation of laboratory values in associati ...200212183800
demographic factors associated with hantavirus infection in bank voles (clethrionomys glareolus).the bank vole (clethrionomys glareolus) is the natural reservoir of puumala virus (puuv), a species in the genus hantavirus. puuv is the etiologic agent of nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome. factors that influence hantavirus transmission within host populations are not well understood. we evaluated a number of factors influencing on the association of increased puuv infection in bank voles captured in a region in northern sweden endemic for the virus. l ...200212194768
behavioral, physiologic, and habitat influences on the dynamics of puumala virus infection in bank voles (clethrionomys glareolus).populations of bank voles (clethrionomys glareolus) were monitored during a 4-year study in southern belgium to assess the influence of agonistic behavior, reproductive status, mobility, and distribution of the rodents on the dynamics of puumala virus (abbreviation: puuv; genus: hantavirus) infection. concordance was high between data from serologic testing and results of viral rna detection. wounds resulting from biting or scratching were observed mainly in adult rodents. hantavirus infection i ...200212194769
human leukocyte antigen-b8-dr3 is a more important risk factor for severe puumala hantavirus infection than the tumor necrosis factor-alpha(-308) g/a polymorphism.the tumor necrosis factor (tnf)-alpha(-308) g/a polymorphism (tnf-2) is in linkage disequilibrium with the human leukocyte antigen (hla)-b8-dr3 haplotype. both factors have been associated with severe puumala hantavirus-induced nephropathia epidemica (ne). to examine which part of this extended haplotype might show the strongest association with the outcome of ne, the hla-b, hla-drb1, and tnf-alpha(-308) alleles in 116 hospital-treated patients with ne were analyzed. the findings pointing to cli ...200212198621
long-lived memory t lymphocyte responses after hantavirus infection.puumala virus (puuv) is a hantavirus that causes hemorrhagic fever with renal syndrome (hfrs), which is an important public health problem in large parts of europe. we examined the memory cytolytic t lymphocyte (ctl) responses in 13 finnish individuals who had hfrs between 1984 and 1995. in seven of these donors, we detected virus-specific ctl responses against the puuv nucleocapsid (n) protein after in vitro stimulation with puuv. six novel cd8(+) ctl epitopes were defined on the n protein and ...200212208874
pcr-generated linear dna fragments utilized as a hantavirus dna vaccine.the field of dna vaccines has grown rapidly, and since most such vaccines involve the inoculation of large circular dna molecules previously propagated in bacteria, several inconveniences (e.g. the presence of antibiotic resistance genes, impurities from bacterial cultures or inefficient uptake of the large and bulky plasmid dna molecules to the nucleus) are debated. in this study, we have explored the possibility of using smaller and more flexible pcr-generated linear dna fragments instead. pho ...200212213408
encephalitis due to a hantavirus infection. 200212217734
hantavirus infections in latvia.in order to investigate the presence of hantavirus infections in latvia, 333 randomly selected human serum samples were screened using an enzyme-linked immunoassay. fifteen samples were positive for hantavirus-specific igg and were subsequently serotyped using a focus reduction neutralization test. fourteen of these samples neutralized at least one of the hantaviruses included in the test, indicating a 4.2% overall seroprevalence in latvia. among 14 focus reduction neutralization test-positive s ...200212226698
[hypopituitarism and hepatitis as complications of nephropathia epidemica]. 200212232982
haemorrhagic fever with renal syndrome in croatia. 200212241810
yeast-expressed puumala hantavirus nucleocapsid protein induces protection in a bank vole model.hantaviruses are rodent-borne agents that cause severe human diseases. the coding sequences for the authentic and a his-tagged puumala hantavirus (puuv) nucleocapsid (n) protein were expressed in yeast (saccharomyces cerevisiae). n-specific monoclonal antibodies demonstrated native antigenicity of the two proteins. all bank voles vaccinated with the his-tagged n protein in freund's adjuvant (n=12) were defined as completely protected against subsequent virus challenge, based on the absence of vi ...200212297397
rodent host specificity of european hantaviruses: evidence of puumala virus interspecific spillover.in order to investigate rodent host specificity of european hantaviruses, experimental infection of colonized and wild-trapped rodents was performed. in addition to the natural rodent reservoir, clethrionomys glareolus, puumala hantavirus (puuv) could infect colonized microtus agrestis and lemmus sibiricus, but not syrian hamsters or balb/c mice. neither c. glareolus, nor m. agrestis, could be readily infected by tula hantavirus (tulv). wild-trapped apodemus flavicollis and a. agrarius, the natu ...200212376967
hantaviruses in estonia.human serum samples collected from healthy individuals in 14 counties were screened by elisa in order to investigate the presence of hantavirus infections in estonia. out of 1,234 serum samples, 124 were found positive for hantavirus-specific igg and were subsequently serotyped by a focus reduction neutralization test. a total of 112 samples neutralized at least one of the examined hantaviruses-puumala (puuv), saaremaa (saav), dobrava (dobv), hantaan, and seoul viruses-and thereby, the focus red ...200212376968
immune parameters in hemorrhagic fever with renal syndrome during the incubation and acute disease: case report.we describe immune parameters in a croatian soldier who presented with mild flu-like symptoms and interstitial inflammatory infiltrate in the lungs on an x-ray during the incubation phase of hemorrhagic fever with renal syndrome (hfrs). enzyme-linked immunosorbent assay (elisa) igm and polymerase chain reaction (pcr) were negative. two weeks later, he developed hfrs caused by the puumala virus. we performed two-color immunofluorescence cytometry with monoclonal antibodies identifying the activat ...200212402402
serological study of hantavirus in man in the autonomous community of madrid, spain.data relating to hantavirus infection in spain are scarce and limited to rural areas. the aim of this work was to study the seroprevalence of hantavirus infection in the autonomous community of madrid (acm), a region containing both rural and urban populations in different ecological settings. sera from 3852 individuals (1849 male, 2003 female) were screened by indirect inmunofluorescence, with vero e6 cells infected with puumala, hantaan and seoul viruses as antigens. screen-positive results we ...200212435066
distribution of hantavirus foci in belgium.during 1999 and 2000, we performed rodent captures on 15 sites all over belgium to evaluate the presence of hantaviruses in local rodent populations. viral antibody and rna detection was performed by elisa/focus reduction neutralisation test and rt-pcr, respectively. we found hantavirus-positive rodents on 13 out of 15 trapping sites and 3 rodent species were found positive for hantavirus infection. apart from puumala virus that was carried by clethrionomys glareolus, 2 additional rodent species ...200212443796
puumala hantavirus infection in humans and in the reservoir host, ardennes region, france.we compared the occurrence of nephropathia epidemica cases, over a multi-annual population cycle, in northeastern france with the hantavirus serology for bank voles captured in the same area. we discuss hypotheses to explain the pattern of infection in both humans and rodents and their synchrony.200212498675
puumala virus infection with multiorgan involvement. 200312536270
diagnostic rapid tests for acute hantavirus infections: specific tests for hantaan, dobrava and puumala viruses versus a hantavirus combination test.hantaviruses infecting humans in eurasia include hantaan, seoul, puumala and the closely related dobrava and saaremaa viruses. these viruses are causative agents of hemorrhagic fever with renal syndrome (hfrs), which is recognized as a severe health care problem in several countries. diagnostics of hantavirus infections relies on serology, performed principally with enzyme immunoassay (eia) or immunofluorescence assay (ifa). we developed four 5-min immunochromatographic igm-antibody tests for di ...200312565162
review of an inactivated vaccine against hantaviruses.hantaviruses cause haemorrhagic fever with renal syndrome and result in severe morbidity and mortality in humans. safe and effective vaccines are needed to reduce the incidence of human illness. in this study, the immune response to an inactivated hantavirus vaccine was measured in 64 human volunteers for hantavax and 10 human volunteers for a hantaan-puumala virus combination vaccine at high risk of infection by virtue of their residence and occupation.200212602351
characterization of expression of puumala virus nucleocapsid protein in transgenic plants.transgenic plants expressing a foreign gene are a suitable system for the production of relevant immunogens in high amounts that can be used for the development of a new generation of vaccines against a variety of infectious diseases. in the present study, the expression of the nucleocapsid (n) protein of hantavirus serotype puumala in tobacco and potato plants was investigated. transgenic tobacco and potato plants were generated and established. these transgenic plants expressed the n protein o ...200212602352
stop codon insertion restores the particle formation ability of hepatitis b virus core-hantavirus nucleocapsid protein fusions.in recent years, epitopes of various origin have been inserted into the core protein of hepatitis b virus (hbc), allowing the formation of chimeric hbc particles. although the c-terminus of a c-terminally truncated hbc (hbc) tolerates the insertion of extended foreign sequences, the insertion capacity is still a limiting factor for the construction of multivalent vaccines. previously, we described a new system to generate hbc mosaic particles based on a read-through mechanism in an escherichia c ...200212602354
[early diagnostics of hemorrhagic fever with renal syndrome on the basis of the use of pumala virus recombinant nucleocapsid protein].pumala virus recombinant nucleocapsid protein was used for the early diagnosis of haemorrhagic fever with renal syndrome. specific igm in the sera of patients could be determined by the iea technique as early as on days 2-3 from the onset of the disease. the diagnostic effectiveness of the test-system was 95% and its specificity was 98%.200312630355
patterns of puumala virus infection in finland.puumala hantavirus infection is prevalent throughout most of europe, and in endemic areas it may be the most common cause of acute renal failure. to evaluate trends in incidence of puumala virus infections in finland, we analysed national surveillance data in 12-month periods from march 1995 to february 2002. during this time, 8184 laboratory-confirmed cases were notified to the national infectious disease register. three epidemic periods were identified, for which the number of cases was more t ...200312631978
distribution of puumala hantavirus in denmark: analysis of bank voles (clethrionomys glareolus) from fyn and jutland.the majority of hantaviral infections in denmark since 1957 have occurred on the island of fyn. we have recently shown the presence of puumala hantavirus (puuv) in bank voles (clethrionomys glareolus) on fyn. to learn more about the distribution and prevalence of puuv in denmark, 310 small mammals, belonging to six rodent and two insectivore species, were trapped in four localities on fyn and three localities on the jutland peninsula (mainland denmark), where only a few cases of nephropathia epi ...200212656129
hantaviruses: a tale of two hemispheres.infectious febrile nephropathies, initially described as epidemics during military campaigns in europe and asia at the turn of the 20(th) century, were eventually all unified under the rubric of hemorrhagic fever with renal syndrome (hfrs) and ascribed to infection from rodent-borne hantaviruses. at the end of the century, hantavirus pulmonary syndrome (hps) was described throughout the americas as a consequence of infection with the new world hantaviruses. the epidemiology and clinical manifest ...200312682619
pulmonary-renal syndrome due to hemorrhagic fever with renal syndrome: an unusual manifestation of puumala virus infection in france.the authors report about a patient who presented with acute respiratory failure, bilateral alveolar infiltrates, without signs of fluid overload, and acute renal failure. percutaneous renal biopsy revealed acute interstitial nephritis with medulla hemorrhages. serologic tests for puumala virus infection were positive. hemorrhagic fever with renal syndrome should be considered when patients present with pulmonary-renal syndrome.200312708571
lymphocyte apoptosis during hemorragic fever with renal syndrome.programmed cell death (pcd) is a fundamental process regulating immune homeostasis. during acute viral infections pcd of lymphocytes by apoptosis is necessary for removing the excess of activated antigen-reactive t cells and down-regulation of the immune response. on the other hand, apoptosis is the key mechanism of elimination of viral-infected cells. at the present time there is virtually no data on mechanisms of immune regulation during human hantavirus infections. in this study we examined t ...200312717553
puumala virus infection with acute disseminated encephalomyelitis and multiorgan failure. 200312737748
expression of the nucleoprotein of the puumala virus from the recombinant semliki forest virus replicon: characterization and use as a potential diagnostic tool.puumala virus (bunyaviridae family, hantavirus genus) causes a mild form of hemorrhagic fever with renal syndrome (hfrs) called nephropathia epidemica in northern and central europe. serological tests are used for diagnosis, but antigen production is difficult because the virus grows poorly in tissue culture. we expressed the n protein (nucleoprotein) of puumala virus via the semliki forest virus (sfv) replicon in mammalian cells and compared its antigenic properties with those of the native ant ...200312853401
hantaviruses induce cytopathic effects and apoptosis in continuous human embryonic kidney cells.hantaviruses are maintained in nature in persistently infected rodents and can also persistently infect cultured mammalian cells, causing little or no cytopathology. an unexpected outcome of this study was the observation of cytopathic effects (cpe) in the hantavirus-infected human embryonic kidney cell line hek293. it was confirmed that hantaviruses induce apoptosis in hek293 cells, although apoptosis appeared mostly in uninfected, bystander cells and rarely in infected hek293 cells. although s ...200312867652
[identification of puumala like viruses in china].to confirm if puumala like viruses exist in china.200312870020
improvement of binding of puumala virus neutralization site resembling peptide with a second-generation phage library.we have previously selected a peptide insert fpcdrlsgywergipspcvr recognizing the puumala virus (puuv) g2-glycoprotein-specific neutralizing monoclonal antibody (mab) 1c9 with kd of 2.85 x 10(-8) from a random peptide library x2cx14cx2 expressed on the piii protein of the filamentous phage fd-tet. we have now created a second-generation phage-displayed peptide library in which each amino acid of the peptide was mutated randomly to another with a certain probability. peptides were selected for hi ...200312874378
hantavirus infections in spain: analysis of sera from the general population and from patients with pneumonia, renal disease and hepatitis.hantaviruses are rodent borne viruses in the family bunyaviridae that cause significant morbidity in large areas of europe. there are only a few reports available on hantavirus infections from spain. although the results of these earlier studies indicated the presence of hantavirus infections, no confirmative or serotype-specific analyses have been performed.200312878094
adaptation of puumala hantavirus to cell culture is associated with point mutations in the coding region of the l segment and in the noncoding regions of the s segment.we previously developed a model for studies on hantavirus host adaptation and initiated genetic analysis of puumala virus variants passaged in colonized bank voles and in cultured vero e6 cells. with the data presented in this paper, the sequence comparison of the wild-type and vero e6-adapted variants of puumala virus, strain kazan, has been completed. the only amino acid substitution that distinguished the two virus variants was found in the l protein, ser versus phe at position 2053. another ...200312885898
[seroepidemiological studies of zoonotic infections in hunters in southeastern austria--prevalences, risk factors, and preventive methods].the aim of this study was to investigate the seroprevalences to zoonotic pathogens in hunters, to propose preventive measures and to obtain more information about the occurrence of zoonotic pathogens in local wild animal populations. from 146 male and 3 female hunters originating from the south-eastern austrian federal states of styria and burgenland blood samples were taken and anamnestic data were obtained using a questionnaire. the serological investigations included the following viral, bact ...200312894685
serological analysis of hemorrhagic fever with renal syndrome (hfrs) patients in far eastern russia and identification of the causative hantavirus genotype.hemorrhagic fever with renal syndrome (hfrs) is endemic in east asia and europe. the disease is caused by several viruses belonging to the genus hantavirus, including the hantaan virus (htnv), seoul virus (seov), dobrava belgrade virus (dobv), and puumala virus (puuv). recently, htnv-related viruses, amur (amr) and far east (fe) genotypes were identified as causative agents of hfrs in far eastern russia. to investigate the epidemiology of hfrs and virus transmission, we collected sera from 17 ac ...200312898330
phylogenetic analysis reveals a low rate of homologous recombination in negative-sense rna viruses.recombination is increasingly seen as an important means of shaping genetic diversity in rna viruses. however, observed recombination frequencies vary widely among those viruses studied to date, with only sporadic occurrences reported in rna viruses with negative-sense genomes. to determine the extent of homologous recombination in negative-sense rna viruses, phylogenetic analyses of 79 gene sequence alignments from 35 negative-sense rna viruses (a total of 2154 sequences) were carried out. powe ...200313679603
quality control measures for the serological diagnosis of hantavirus infections.with society's rapidly increasing mobility, patients infected with severe viral infections can become seriously ill at any place in europe and elsewhere. improving the diagnostics of these infections is the most important step in detecting the pathogens and dealing with them, and for this purpose, quality control measures are essential tools.200314522063
genetic similarity of puumala viruses found in finland and western siberia and of the mitochondrial dna of their rodent hosts suggests a common evolutionary origin.a total of 678 small mammals representing eight species were trapped in western siberia in 1999-2000 and assayed for the presence of hantaviruses. eighteen animals, all clethrionomys species, were antigen positive by enzyme-linked immunosorbent assay (elisa). small and medium genome segments were recovered by rt-pcr from six samples from clethrionomys glareolus and three from clethrionomys rufocanus. sequence comparison and phylogenetic analysis revealed that these hantaviruses were puumala viru ...200314636686
development of an efficient method for recovery of puumala and puumala-related viruses by inoculation of mongolian gerbils.puumala (puu) virus and puu-related viruses are difficult to isolate in cell culture. to determine whether animal inoculation would be a better alternative for virus recovery, the sotkamo strain of puu virus was inoculated into several animal species. newborn mongolian gerbils (mgs), mice, and rats were infected with the sotkamo strain by intracerebral (ic), intraperitoneal (ip), and subcutaneous (sc) inoculation. antibodies to puu appeared in mgs at 30 days post-infection (dpi), and in mice and ...200314665747
human hantavirus infections, sweden.the prevalent human hantavirus disease in sweden is nephropathia epidemica, which is caused by puumala virus and shed by infected bank voles (clethrionomys glareolus). to evaluate temporal and spatial patterns of this disease, we studied 2,468 reported cases from a highly disease-endemic region in northern sweden. we found that, in particular, middle-aged men living in rural dwellings near coastal areas were overrepresented. the case-patients were most often infected in late autumn, when engaged ...200314718081
bovine aortic endothelial cells are susceptible to hantavirus infection; a new aspect in hantavirus ecology.hantaviruses are enveloped rna viruses that belong to the family bunyaviridae. they are the causative agents of hemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps). hantaviruses show a worldwide distribution with specific rodent species as natural hosts. it is known that rodents can transmit the virus via feces, urine, saliva, or bites to humans. additionally, antibodies against different hantaviruses were also found in domestic animals, for example, danes et al. ...200414972540
microarray technology for identification and distinction of hantaviruses.dna microarrays combine high-precision technology with advanced molecular biology to achieve high-throughput screening of dna fragments. in this study, we investigated the potential of the cdna microarray technique to identify and discriminate pcr derived amplicons from genetically highly similar viruses. the wide range of sequence variation among hantaviruses makes them suitable as a model for this purpose. the hantaviruses, carried by rodents, cause several hundred thousand cases of severe hum ...200414981768
[the biggest epidemic of hemorrhagic fever with renal syndrome in croatia].the largest outbreak of hemorrhagic fever with renal syndrome (hfrs) to date occurred in croatia in the year 2002. the epidemic started in winter, lasted throughout spring to summer months, ending not earlier than november.200315011458
[grading the severity of disease in patients with puumala or dobrava virus infections from 1995 to 2000 in croatia].the aim of our study was to evaluate the proposed croatian scale for grading the disease severity in patients with hemorrhagic fever with renal syndrome (hfrs). the aim was also to determine whether the infection with dobrava virus (dobv) in croatia was associated with a more severe illness than the infection with puumala virus (puuv).200315011460
[puumala and dobrava viruses in the northeastern and central regions of bosnia].bosnia and herzegovina has been known as a highly endemic region for hantavirus infections for more than 50 years. previous studies have shown that at least two different hantaviruses, the murine dobrava (dob) and avricoline puumala (puu) viruses, each carried by a different rodent species, have been circulating in the area. however, there is little information on rodent population density fluctuations in bosnia over the past years as well as on the ratio of puumala to dobrava infection in human ...200315011464
[serologic diagnosis of hemorrhagic fever with renal syndrome in bosnia and herzegovina in 2002].results of the serologic confirmation of hemorrhagic fever with renal syndrome (hfrs) in patients with clinical picture and overt symptoms of the disease from particular areas in bosnia and herzegovina during 2002 are presented.200315011465
[hemorrhagic fever with renal syndrome: imported or native disease in the zadar region].the aim of the study is to warn of the need of clinical hemorrhagic fever with renal syndrome (hfrs) recognition and determination, and of the risk of its spread from a new focus of this natural zoonosis near zadar (north dalmatia), i.e., in the northern part (lika) of the zadar county.200315011474
segments of puumala hantavirus nucleocapsid protein inserted into chimeric polyomavirus-derived virus-like particles induce a strong immune response in mice.insertion of a short-sized epitope at four different sites of yeast-expressed hamster polyomavirus major capsid protein vp1 has been found to result in the formation of chimeric virus-like particles. here, we demonstrate that the insertion of 45 or 120 amino acid-long segments from the n-terminus of puumala hantavirus nucleocapsid protein into sites 1 (amino acids 80-89) and 4 (amino acids 288-295) of vp1 allowed the highly efficient formation of virus-like particles. in contrast, expression lev ...200415018662
bovine aortic endothelial cells are susceptible to hantaan virus infection.hantavirus serotype hantaan (htn) is one of the causative agents of hemorrhagic fever with renal syndrome (hfrs, lethality up to 10%). the natural host of htn is apodemus agrarius. recent studies have shown that domestic animals like cattle are sporadically seropositive for hantaviruses. in the present study, the susceptibility of bovine aortic endothelial cells (baec) expressing alpha(v)beta(3)-integrin to a htn infection was investigated. viral nucleocapsid protein and genomic rna segments wer ...200415033559
immune responses to puumala virus infection and the pathogenesis of nephropathia epidemica.puumala virus, causative agent of a mild form of hemorrhagic fever with renal syndrome, also known as nephropathia epidemica, induces long-lasting humoral and cellular immunity in patients. the virus itself is not cytopathic, and the immune responses to the virus may be involved in teh pathogenesis of the disease.200415049335
robust filtering and particle picking in micrograph images towards 3d reconstruction of purified proteins with cryo-electron microscopy.in order to make a high resolution model of macromolecular structures from cryo-electron microscope (cryo-em) raw images one has to be precise at every processing step from particle picking to 3d image reconstruction. in this paper we propose a collection of novel methods for filtering cryo-em images and for automatic picking of particles. these methods have been developed for two cases: (1) when particles can be identified and (2) when particle are not distinguishable. the advantages of these m ...200415065672
modes of hantavirus transmission in a population of clethrionomys rufocanus bedfordiae inferred from mitochondrial and microsatellite dna analyses.to elucidate the mode of transmission of puumala-related hantavirus in a population of gray red-backed voles, clethrionomys rufocanus bedfordiae, in hokkaido, japan, we analyzed the kin structure and dispersal patterns of individual voles using microsatellite and mitochondrial dna markers. siblings or dam/offsprings was identified within the population based on the relatedness calculation with the microsatellite data. the pairwise relatedness values obtained could reveal kinship among all vole i ...200415098108
urinary excretion of interleukin-6 correlates with proteinuria in acute puumala hantavirus-induced nephritis.nephropathia epidemica (ne) is a mild type of hemorrhagic fever with renal syndrome caused by puumala hantavirus. cytokines are thought to have an important role in the pathogenesis of ne. the aim of this study is to evaluate whether cytokines contribute to renal involvement in ne.200415112171
saaremaa hantavirus in denmark.most human hantavirus infections in denmark have been registered on the fyn island with puumala hantavirus hosted by clethrionomys glareolus as the causative agent. to search for other known european hantaviruses in denmark, we analyzed 101 apodemus spp. mice trapped on the lolland island. genome sequences of saaremaa hantavirus (saav) were recovered from one of the a. agrarius, thus suggesting saav presence in denmark. we also analyzed serum samples from a patient from lolland with a history of ...200415135745
[glomerular-type proteinuria in hantavirus nephritis].infection with hantavirus of the puumala type is known to cause severe illness, fever, loin pain and impaired vision. tubulointerstitial nephritis leads to acute renal failure.200415146285
an amino-terminal segment of hantavirus nucleocapsid protein presented on hepatitis b virus core particles induces a strong and highly cross-reactive antibody response in mice.previously, we have demonstrated that hepatitis b virus (hbv) core particles tolerate the insertion of the amino-terminal 120 amino acids (aa) of the puumala hantavirus nucleocapsid (n) protein. here, we demonstrate that the insertion of 120 amino-terminal aa of n proteins from highly virulent dobrava and hantaan hantaviruses allows the formation of chimeric core particles. these particles expose the inserted foreign protein segments, at least in part, on their surface. analysis by electron cryo ...200415165823
acute non-cardiogenic pulmonary edema in a 2003 french puumala virus case: cautions and corrections. 200415182134
rapid field test for detection of hantavirus antibodies in rodents.puumala virus (puuv) is the causative agent of nephropathia epidemica, a mild form of haemorrhagic fever with renal syndrome. puuv is transmitted to humans via aerosolized excreta of the infected bank vole (clethrionomys glareolus). current methods for screening of the puuv prevalence among bank vole populations are laborious, combining sampling in the field and subsequent analyses in the laboratory. in order to facilitate animal testing, a new serological immunochromatographic rapid test was de ...200415188724
puumala virus nucleocapsid protein expressed in transgenic plants is not immunogenic after oral administration.transgenic plants expressing foreign genes are suitable systems for the production of relevant immunogens in high amounts that can be used to develop a new generation of vaccines against a variety of infectious diseases. transgenic tobacco and potato plants expressing the nucleocapsid protein of hantavirus serotype puumala were generated and established. puumala virus is a human pathogen causing hemorrhagic fever with renal syndrome. to investigate oral immunogenicity of the nucleocapsid protein ...200415215689
identification and analysis for cross-reactivity among hantaviruses of h-2b-restricted cytotoxic t-lymphocyte epitopes in sin nombre virus nucleocapsid protein.sin nombre virus (snv) causes hantavirus pulmonary syndrome (hps), with a high rate of mortality in humans who are infected by the transmission of virus from the natural rodent host. in humans, cytotoxic t lymphocytes (ctl) specific for snv appear to play an important role in the pathogenicity of hps. there is a correlation between the frequencies of snv-specific ctls and the severity of hps disease. in order to create a mouse model to study the role of snv-specific t cells in vivo, t cell respo ...200415218176
high yields of stable and highly pure nucleocapsid proteins of different hantaviruses can be generated in the yeast saccharomyces cerevisiae.recently, the high-level expression of authentic and hexahistidine (his)-tagged puumala (strain vranica/hällnäs) hantavirus nucleocapsid protein derivatives in the yeast saccharomyces cerevisiae has been reported [dargeviciute et al., vaccine, 20 (2002) 3523-3531]. here we describe the expression of his-tagged nucleocapsid proteins of other puumala virus strains (sotkamo, kazan) as well as dobrava (strains slovenia and slovakia) and hantaan (strain fojnica) hantaviruses using the same system. al ...200415246668
detection of puumala hantavirus antibody with elisa using a recombinant truncated nucleocapsid protein expressed in escherichia coli.a truncated recombinant nucleocapsid protein (rnp118) consisting of the first 118 amino-terminal amino acids (aa) of the puumala hantavirus (puuv) nucleocapsid protein expressed in escherichia coli, was evaluated for its antigenicity and reliability as serodiagnostic antigen in an enzyme-linked immunosorbent assay (elisa) for detection of puuv antibodies in human sera. the puuv nucleocapsid protein has been shown to contain several b-cell epitopes, mapped within the first 118 amino-terminal aa. ...200415279709
characterization of tula virus from common voles (microtus arvalis) in poland: evidence for geographic-specific phylogenetic clustering.tula virus (tulv), a recently identified arvicolid rodent-borne hantavirus, is harbored by the european common vole (microtus arvalis) in central russia and the czech and slovak republics. we report the isolation and characterization of this hantavirus from m. arvalis captured in poland, a country where human disease caused by hantaviruses has not been recognized. of 34 arvicolid rodents (24 clethrionomys glareolus, 9 m. arvalis, 1 pitymys sp.) captured in lodz and tuszyn, poland, during june to ...200415284484
complete gene sequence of a human puumala hantavirus isolate, puumala umeå/hu: sequence comparison and characterisation of encoded gene products.puumala virus is a member of the hantavirus genus in the bunyaviridae family, and the major causative agent of haemorrhagic fever with renal syndrome in europe. this study was conducted with a human puumala virus isolate (puuv umeå/hu), and contains the determination of the first complete puuv sequence from a human source. when the relationship to other puumala viruses was analysed, a possible rna segment exchange between two local strains of puuv was noticed. furthermore, the coding regions of ...200415351488
delayed viremia and antibody responses in puumala hantavirus challenged passively immunized cynomolgus macaques.no specific therapy is currently available against hemorrhagic fever with renal syndrome (hfrs) or hantavirus pulmonary syndrome. in order to study if passive immunization could inhibit hantavirus infection and/or symptoms, we inoculated two cynomolgus macaques with neutralizing monoclonal antibodies and subsequently challenged them with wild-type puumala virus (puuv), recently shown to induce typical signs of milder hfrs in cynomolgus macaques. although viral load and antibody titers did not di ...200515449139
[amplification test-systems in the diagnosis of hemorrhagic fever with renal syndrome and in studies of viral pathogens].the "vectohantivirus-ampli" test system based on rtpcr was shown as fitting the detection of virus rna in blood samples of patients with hemorrhagic fever with renal syndrome (hfrs) made at early stages and no later than 7 days from the disease onset. a sequence analysis of viral nucleotide sequences of pcr products produced by the test-system ensured the identification of hantaviruses (pathogens of hfrs). two genetic variants of puumula virus were shown to circulate in the territory of the bash ...200415455692
hantavirus puumala infection as a cause of fever of unknown origin in a child.hantavirus infection due to puumala virus causes nephropathica epidemica, a disorder characterized by fever, haematological abnormalities, mild renal dysfunction and ophthalmological abnormalities. the prevalence in most european countries is low, but the virus can be endemic. in children, hantavirus infection is rare. this paper describes a young girl diagnosed with hantavirus infection. the patient presented with high fever, proteinuria, haematuria and eye lesions, but other typical hallmarks ...200415456206
thrombocytopenia and acute renal failure in puumala hantavirus infections.nephropathia epidemica, caused by puumala virus (puuv) infection, is a form of hemorrhagic fever with renal syndrome of variable severity. early prognostic markers for the severity of renal failure have not been established. we evaluated clinical and laboratory parameters of 15 consecutive patients with acute puuv infection, which is endemic in the alb-danube region, south germany. severe renal failure (serum creatinine >620 micromol/l) was observed in seven patients; four required hemodialysis ...200415496243
[sero-epidemiological studies of zoonotic infections in hunters--comparative analysis with veterinarians, farmers, and abattoir workers].the aim of this study was to investigate seroprevalences to zoonotic pathogens in hunters, to compare the results with other predisposed occupational groups already investigated and to propose preventive measures. blood samples were taken from 146 male and 3 female hunters from the provinces of styria and burgenland in the south-east of austria and anamnestic data were obtained using a questionnaire. the serological investigations included the following bacterial, viral and parasitic zoonotic ag ...200315508783
the clinical usefulness of a puumalavirus recombinant nucleocapsid protein based enzyme-linked immunosorbent assay in the diagnosis of nephropathia epidemica as compared with an immunofluorescence assay.nephropathia epidemica (ne), a hemorrhagic fever with renal syndrome (hfrs) predominantly encountered in northern europe, is a febrile disease, commonly associated with acute renal impairment. a rapid and reliable serological diagnosis is required to differentiate ne from other acute febrile illnesses in endemic areas.199615566886
[a new genetic variant of the puuv virus from the maritime territory and its natural carrier red-grey vole clethrionomys rufocanus].pulmonary tissues of red-grey voles, clethrionomys rufocanus from shkotovo district and maritime territory were investigated. rt-pcr was used to detect the hantavirus nt-222 m-segment genome and nt-403 mitochondrial dna fragment. a new genetic variant of the puuv virus named as "shkotovo", that is different from other puuv strains by 18-23%, was shown to be circulating in red-grey voles. a phylogenetic analysis denoted 2 puuv subgroups with their rodent-host branching into c. graleolus and c. ru ...200415597959
human leukocyte antigens b8-drb1*03 in pediatric patients with nephropathia epidemica caused by puumala hantavirus.in adults, hla haplotype b8-drb1*03 is clearly associated with a severe clinical course of nephropathia epidemica caused by puumala hantavirus. we investigated whether the same applies in pediatric patients. this hla haplotype was found in 20 of 39 (51%) of the patients, a significantly higher figure than in the finnish population (19%). there were, however, no significant differences in the clinical picture between patients with and without hla b8-drb1*03.200415602199
identification of dobrava, hantaan, seoul, and puumala viruses by one-step real-time rt-pcr.we developed four assays for specifically identifying dobrava (dob), hantaan (htn), puumala (puu), and seoul (seo) viruses. the assays are based on the real-time one-step reverse transcriptase polymerase chain reaction (rt-pcr) with the small segment used as the target sequence. the detection limits of dob, htn, puu, and seo assays were 25, 25, 25, and 12.5 plaque-forming units, respectively. the assays were evaluated in blinded experiments, each with 100 samples that contained andes, black cree ...200415664046
nucleocapsid protein of cell culture-adapted seoul virus strain 80-39: analysis of its encoding sequence, expression in yeast and immuno-reactivity.seoul virus (seov) is a hantavirus causing a mild to moderate form of hemorrhagic fever with renal syndrome that is distributed mainly in asia. the nucleocapsid (n) protein-encoding sequence of seov (strain 80-39) was rt-pcr-amplified and cloned into a yeast expression vector containing a galactose-inducible promoter. a survey of the pattern of synonymous codon preferences for a total of 22 n protein-encoding hantavirus genes including 13 of seov strains revealed that there is minor variation in ...200515744561
detection of human hantavirus infections in lithuania.in europe certain hantaviruses are known to cause hemorrhagic fever with renal syndrome of different severity. the objective of the present investigation was to study the presence of hantavirus infections in lithuania.200515827873
[hantavirus infections].hantaviruses are cosmopolite anthropozoonosis considered as an emerging disease. four pathogenic types for humans and part of the bunyaviridae species are hosted by rodents and have been isolated: the sin nombre virus responsible for the severe american respiratory form; the hantaan and seoul viruses responsible for hemorrhagic fevers with renal syndrome (hfrs) of severe to moderate expression in asia and also in the balkans; the puumala virus responsible for hfrs of moderate expression or the s ...200515859577
development and evaluation of serological assays for detection of human hantavirus infections caused by sin nombre virus.the hantavirus cardiopulmonary syndrome (hcps) was first recognized in 1993 after a cluster of acute respiratory distress syndrome deaths in the southwestern of the united states. the major causative agent of hcps in north america is the sin nombre virus (snv) carried by the deer mouse peromyscus maniculatus. the first hcps case imported to europe was reported in 2002.200515911448
[the renal failure and capillary leak during the acute stage of (dobrava) dob and puu (puumala) infection].the target organ for puumala (puu) and dobrava (dob) viruses is the kidney, but the impact on renal function seems far more important in dob infection than in puu infections. aim of study was to estimate the renal failure and capillary leak during the acute stage of dob-infection and puu-infection. 50 patients with serological conformed diagnosis of acute hantavirus infection were included in the study. diuresis, serum urea and creatinine were measured. size of kidneys and presence of ascites wa ...200516018388
hemorrhagic fever with renal syndrome in the pomurje region of slovenia--an 18-year survey.to determine the etiology of hemorrhagic fever with renal syndrome (hfrs) in the north-eastern part of slovenia (pomurje region) together with demographic, epidemiological and clinical data on 25 patients from this region who were diagnosed and treated at the general hospital in murska sobota between 1986 and 2003.200516053195
puumala virus in croatia in the 2002 hfrs outbreak.hfrs is an endemic disease throughout croatia. the incidence of hfrs varies in a cyclic fashion, with peaks occurring every couple of years, coinciding with peaks in vole populations. puuv was shown to be dominant pathogen during the last hfrs outbreak in croatia in 2002. we focused our research on two newly discovered localities (okucani and nova gradiska) with a high number of reported hfrs cases and a significant increase in rodent population. puuv infection was verified in 84.2% of patients ...200516121366
hantavirus and arenavirus antibody prevalence in rodents and humans in trentino, northern italy.the spatial and temporal distribution of hantavirus and arenavirus antibody-positive wild rodents in trentino, italy, was studied using immunofluorescence assays (ifa) in two long-term sites trapped in 2000-2003, and six other sites trapped in 2002. the overall hantavirus seroprevalence in the bank voles, clethrionomys glareolus (n=229) screened for puumala virus (puuv) antibodies was 0.4%, and that for apodemus flavicollis mice (n=1416) screened for dobrava virus (dobv) antibodies was 0.2%. ant ...200616371172
habitat factors associated with bank voles (clethrionomys glareolus) and concomitant hantavirus in northern sweden.puumala virus (puuv), genus hantavirus, causes nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome in humans. in this study, bank voles, the natural reservoir of puuv, were captured at locations of previous human puuv exposure and paired controls within a region of high incidence in northern sweden. the aim of the study was to evaluate the influence of environmental factors on the abundance of bank voles and the occurrence of puuv. the total number of voles and the numbe ...200516417427
serological assays for the detection of human andes hantavirus infections based on its yeast-expressed nucleocapsid protein.the objective of the study was to develop and evaluate igm and igg elisas and an igg western blot test for the serological detection of human infections with andes virus (andv), the major cause of hantavirus cardiopulmonary syndrome (hcps) in south america.200616428893
a novel method for cloning of non-cytolytic viruses.hantaviruses are rodent-borne pathogens with a segmented single-stranded rna genome of negative polarity. spontaneous occurrence of variants with genetic heterogeneity have been observed both in vivo and in vitro. the objective of this study was to establish a method for the cloning of genetically homogenous hantaviruses which can be used for subsequent functional studies. infected veroe6 cells were incubated with an agarose/medium overlay to prevent uncontrolled distribution of de novo synthesi ...200616504312
production of hantavirus puumala nucleocapsid protein in saccharomyces cerevisiae for vaccine and diagnostics.the production of hantavirus puumala nucleocapsid (n) protein for potential applications as a vaccine and for diagnostic purposes was investigated with saccharomyces cerevisiae as a recombinant host. the n protein gene and the hexahistidine tagged n (h-n) protein gene were expressed intracellular from a 2-microm plasmid vectors under the control of a fused galactose inducible gal10-pyk promoter. for monitoring the recombinant gene expression, a h-n and a gfp fusion protein was used. different cu ...200616513199
generation of monoclonal antibodies of desired specificity using chimeric polyomavirus-derived virus-like particles.foreign protein sequences presented on hamster polyomavirus (hapyv) major capsid protein vp1-derived virus-like particles (vlps) have been demonstrated to be highly immunogenic. the current study was aimed to evaluate vp1-derived chimeric vlps as tools for hybridoma technology to generate monoclonal antibodies (mabs) of desired specificity. chimeric vlps containing inserts of different size and origin were used as immunogens. chimeric vlps carrying a 9 amino acid (aa)-long cytotoxic t-cell epito ...200616516908
corticosteroids combined with continuous veno-venous hemodiafiltration for treatment of hantavirus pulmonary syndrome caused by puumala virus infection.reported here are two cases of hantavirus pulmonary syndrome caused by puumala virus infection, which rapidly resolved after initiation of corticosteroid treatment combined with continuous veno-venous hemodiafiltration. these cases emphasize the role of the inflammatory response in the pathogenesis of hantavirus pulmonary syndrome.200616550348
short report: dual infections with puumala virus and leptospira interrogans serovar lora in a bank vole (clethrionomys glareolus).leptospirosis and hemorrhagic fever with renal syndrome are public health problems in croatia. diagnosis and epidemiology of these diseases are complicated because these two diseases are sympatric in certain areas. we describe a natural dual infection of puumala virus and a leptospire in a bank vole (clethrionomys glareolus).200616606994
ten-year prognosis of puumala hantavirus-induced acute interstitial nephritis.nephropathia epidemica (ne) is a hemorrhagic fever with renal syndrome caused by puumala hantavirus. its long-term prognosis is considered favorable. there are, however, some reports about subsequent hypertension, glomerular hyperfiltration, and proteinuria after previous hantavirus infection. therefore, we studied 36 patients 5 and 10 years after acute ne, with 29 seronegative controls. office blood pressure, ambulatory 24-h blood pressure (abp), glomerular filtration rate (gfr), and proteinuri ...200616641933
a new puumala hantavirus subtype in rodents associated with an outbreak of nephropathia epidemica in south-east germany in 2004.a micro-epidemic of hantavirus infections occurred in lower bavaria, south-east germany, starting in april 2004. while only three cases were registered from 2001 to 2003, a dramatically increased number of clinically apparent human hantavirus infections (n=38) was observed in 2004, plus seven additional cases by june 2005. to determine the reservoir responsible for the infections, a total of 43 rodents were trapped in lower bavaria. serological and genetic investigations revealed that puumala vi ...200616650330
is there an increased long-term risk of hypertension and renal impairment after puumala virus-induced nephropathy?nephropathia epidemica (ne) is a mild form of hemorrhagic fever with renal syndrome, assumed to have a favorable prognosis. ne patients who manifested a higher glomerular filtration rate and mean systolic blood pressure, and more proteinuria, versus controls at 5 years of follow-up demonstrated no major abnormalities after 10 years. antihypertensive treatment was, however, more common. could ne predispose some patients to develop hypertension after all?200616724089
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